An OHSS – Free Clinic

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An OHSS – Free Clinic

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An OHSS – Free Clinic

  1. 1. An OHSS – Free Clinic Aboubakr elnashar Benha university Hospital, Egypt elnashar53@hotmail.com Aboubakr Elnashar
  2. 2. Contents OHSS Definition Incidence Pathophysiology Risk factors Types Degrees Complications Prevention  Conclusions OHSS free clinic I. GnRHan protocol II. GnRHa triggering III.Freeze all IV.Replacement in natural or artificial cycle Aboubakr Elnashar
  3. 3. OHSS Define Systemic synd resulting from vasoactive products released by hyperstimulated ovaries. An iatrogenic complication of ovarian stimulation. Life threatening Aboubakr Elnashar
  4. 4. Incidence Mild: common, up to 33% of IVF Moderate: 5% (Delvigne, 2009). Mod to Severe: 3–8% of IVF cycles Cases requiring hospitalization: 2% (Papanikolaou et al., 2005). Varies: 1. Treatments 2. Patient 3. Classification schemes Aboubakr Elnashar
  5. 5. An increase in the incidence of Severe forms of OHSS Patients hospitalized (Abramov et al., 1999; Cunha-Filho et al., 2003). Aboubakr Elnashar
  6. 6. Pathophysiology Inc cap permeability: leakage of fluid from vas compartment: - 3rd space fluid accumulation -IV dehydration. Aboubakr Elnashar
  7. 7.  RISK FACTORS The most important: PCOS & history of OHSS  Prior to an IVF cycle Young age (22 y), lean (BMI, 19 kg/m2), PCOS History of: High response during a previous COS Cycle cancellation related to high response Development of moderate or severe OHSS (Ragni et al, 2005; Griesinger et al, 2007; Imbar et al, 2012) Basal investigations (NICE, 2013) Total AFC > 16 AMH>3.5 ng/ml (25.0 pmol/l) FSH<4 IU/l Aboubakr Elnashar
  8. 8. During IVF: One of the following Peak E2 > 3000-4000 pg/mL, 20 follicles at least 10 mm, in addition to the leading follicles on the day of hCG Retrieval of >15 oocytes (Ragni et al, 2005; Griesinger et al, 2007; Imbar et al, 2012) For GnRHan protocol: 18 follicles 11 mm on the day of hCG: 83% specificity in predicting severe OHSS (Papanikolaou et al.,2006) Aboubakr Elnashar
  9. 9. Types (Esteve, 2013)Aboubakr Elnashar
  10. 10. CriticalSevereModerateMild •Tense ascites •Oligo/anuria •Thromboembolism •ARDS • Ascites •Oliguria •Mod ab pain •N± V •Ab bloating •Mild ab pain Cl •large hydrothorax•±hydrothorax •Ov›12 cm* •Ascites •Ov: 8–12 cm* Ov: ‹8 cm*US •Hct›55% •WCC›25 000/ml •Hct ›45% •Hypoproteina emia Lab •ICU•In ptOut pt, In pt: unable to control pain, N with oral tt, Difficulties in monitoring Out ptTT Degrees: Mathur, 2oo5 Aboubakr Elnashar
  11. 11. Complications Morbidity 1. Thrombosis 2. Renal& liver dysfunction 3. ARDS 4. Psychological burden & their willingness to undergo further fertility tt (Verberg et al., 2008). 5. Pregnancy-related complications Miscarraige, PTL, PIH (Abramov et al., 1998; Courbiere et al., 2011). Aboubakr Elnashar
  12. 12. Obstetrical outcome of IVF pregnancies in OHSS Occurrence 40/3 504 cycles (1.4 %) Control (80) P Duration of hospitalization 10 Days 0 Early OHSS 22.5 % 0 Late OHSS 75.5 % 0 Thrombo-embolic complications 10.0 % 0 Pregnancy induced hypertension 21.0 % 9 % S Preterm labor 36.0 % 11 % S Courbiere, 2011 Aboubakr Elnashar
  13. 13. Mortality  Causes of mortality in OHSS 1. ARDS 2. Cerebral infarction 3. Hepatorenal failure Aboubakr Elnashar
  14. 14. True incidence: unk Worldwide: Far greater Underestimated (Bewley et al 2011)  Mortality from OHSS: unacceptable. The introduction of OHSS-Free Clinics cannot be postponed (Devroey and Adriaensen, 2011). Aboubakr Elnashar
  15. 15. Prevention I. Modified stimulation protocols 1. HCG a. HCG Withholding b. Delaying HCG (Coasting or drifting) c. Decrease HCG dose 2. HMG a. Lower doses of gonadotrophins b. Chronic low dose step up protocol 3. GnRHa to trigger ovulation 4. GnRHan rescue by replacing a GnRHa with a GnRHan Aboubakr Elnashar
  16. 16. II. Modified techniques 1. Follicular aspiration before or after hCG 2. Cryopreservation of embryos 3- Selective oocyte retrieval in spontaneous conception cycles 4. Ovarian electrocautery III. Adjuvant 1. IV albumin 2. 6% Hydroxyethyl starch 3. Metformin 4. Dopamin agonist Aboubakr Elnashar
  17. 17. We have to change totally the concept of IVF to obtain an OHSS Free Clinic Aboubakr Elnashar
  18. 18.  GnRHan protocol instead of long protocol  Ovulation Triggering with GnRHa instead of HCG trigger  Vitrification of all oocytes and/ or embryos  ET in frozen – thawed cycle Proposed Protocol of Zero% OHSS: 4 Steps Aboubakr Elnashar
  19. 19. I. The use of the GnRHan protocol inhibition of the premature LH surge {an immediate action}: administered only when there is a need for suppressing the LH surge (Reissmann et al., 2000). Patient-friendly protocol (Lambalk et al., 2006). Fewer injections Short duration of stimulation Absence of side effects caused by profound hypoestrogenaemia (Borm and Mannaerts, 2000; Fluker et al.,2001). Aboubakr Elnashar
  20. 20. No clinically significant difference in live birth rates between GnRHan and agonists (M A, Al-Inany et al., 2011). Significantly lower incidence of OHSS compared with GnRHa (Tarlatzis and Kolibianakis, 2007). Aboubakr Elnashar
  21. 21. II. Ovulation triggering with GnRHa instead of HCG trigger GnRHan: significant reduction of severe OHSS, but cannot eliminate the syndrome HCG triggering: gold standard {long half-life (30 H) with serum hCG detectable up to 14 days after the injection}: increased incidence of OHSS (Gonen et al., 1990). Triggering with 5000 or 10 000 IU: effective ±severe OHSS (Kolibianakis et al., 2007). Aboubakr Elnashar
  22. 22. GnRHa triggering (triptorelin 0.2 mg) breakthrough in the elimination of OHSS (Itskovitz et al., 1991; Shalev et al., 1994).  Effective alternative to hCG (Segal and Casper, 1992). Incidence of OHSS: 0% (Melo et al., 2009). Aboubakr Elnashar
  23. 23. Disadvantages luteal phase defect (Segal and Casper, 1992). :PR significantly decreased (Humaidan et al., 2005; Kolibianakis et al., 2006). {negative effect on: function of the corpus luteum function of the endometrium} (Humaidan et al., 2005, 2009). Aboubakr Elnashar
  24. 24. To correct the luteal phase and pregnancy rates Intensive luteal phase support (luteal phase rescues) 1. IM progesterone combined with E2 patches (Engmann et al., 2008; Diluigi et al., 2010). 2. 1500 units of hCG at oocyte retrieval (Humaidan et al., 2006, 2010). Aboubakr Elnashar
  25. 25. III. Cryopreservation of oocytes and/or embryos Freeze-all strategy: An alternative to luteal phase rescues in GnRHan and GnRHa combination stimulation cycles 1. Oocyte cryopreservation Best option for patients with increased risk for OHSS. Excellent oocyte survival rates (Kuwayama et al., 2005; Cobo et al., 2008; Nagy et al., 2009). Aboubakr Elnashar
  26. 26. Fertilization, embryo development and CPR: comparable when using fresh or vitrified oocytes (Rienzi et al., 2010; (Cobo et al., 2010). CPR as high as 80% (Kim et al., 2010). Significantly higher CPR compared with coasting (50% Vs 30%) (Herrero et al., 2011). An option for couples who do not desire embryo cryopreservation [ethical concerns} (Heng, 2007). Aboubakr Elnashar
  27. 27. 2. Embryo cryopreservation Safe alternative for patients at risk for OHSS. Similar CPR whether using elective cryopreservation of all embryos or fresh embryo transfer (Ferraretti et al., 1999; Aflatoonian et al., 2010; Surrey et al., 2010). Vitrification: an efficient method for patients at risk for OHSS (Selman et al., 2009). Aboubakr Elnashar
  28. 28. No difference in live birth rates between fresh and frozen/thawed cycles (Centre for Disease Control and Prevention, 2008). Significantly higher embryo survival and subsequent development rates (Balaban et al., 2008). Aboubakr Elnashar
  29. 29. IV. Replacement of an embryo after thawing in natural or artificial cycle 1. Natural cycles: with or without hCG administration (Fatemi et al., 2010), 2. Artificial cycle: Exogenous E2 and progesterone, with or without the addition of GnRHa (Surrey et al., 2010). GnRH a (Day 21) + E2 + progesterone from OPU Day Aboubakr Elnashar
  30. 30. Conclusion The balance between the desire for pregnancy and the patients’ safety is a top priority. Mortality from OHSS: unacceptable. Aboubakr Elnashar
  31. 31. The strategy to obtain an OHSS-Free Clinic is closely related to the segmentation concept. Segment A: Optimization of ovarian stimulation by GnRHa triggering in a GnRHan cycle Segment B: Optimization of embryology by oocyte and/or embryo vitrification Segment C: Optimization of endometrial implantation by embryo replacement in a receptive endometrium in a natural or artificial cycle. Aboubakr Elnashar
  32. 32. Thank you Face book: Aboubakr Elnashar lectures Aboubakr Elnashar
  33. 33. Yesterday  GnRHa  HCG for triggering  Fresh ET after progesterone in luteal phase  Replacement in natural or artificial cycle  OHSS: 2 % Today  GnRHan  GnRHa triggering if at risk for OHSS  Freeze all  Fresh ET after progesterone and low dose hCG in luteal phase  Replacement in natural or artificial cycle  OHSS: 0 % Aboubakr Elnashar

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